Active tuberculosis causes lung cavities where TB-bacteria grow to high levels. Cavitary TB is more transmissible to others, harder to treat in the patient who has it, and more likely to lead to drug resistance. This proposal will combine an animal model in which TB cavities reproducibly develop with novel radiologic imaging technologies and traditional pharmacologic tools to determine whether the TB cavity serves as a sanctuary site where bacteria may escape high drug concentrations and develop resistance. The last part of the study will determine whether giving immunosuppressive drugs which block cavity development together with antibiotics is useful in accelerating cure in an animal model of TB.